PMID- 9581815
OWN - NLM
STAT- MEDLINE
DCOM- 19980602
LR  - 20201113
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 58
IP  - 9
DP  - 1998 May 1
TI  - Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and 
      primitive neuroectodermal tumors of the central nervous system.
PG  - 1798-803
AB  - About one-third of sporadic basal cell carcinomas (BCCs) of the skin and 10-15% 
      of primitive neuroectodermal tumors (PNETs) of the central nervous system show 
      mutations in the PTCH tumor suppressor gene. The PTCH gene product (Ptch) 
      functions as a transmembrane receptor for the Sonic hedgehog protein (Shh) and 
      interacts with another transmembrane protein called Smoh. To further elucidate 
      the significance of alterations in the Shh signaling pathway, we investigated 31 
      sporadic BCCs and 15 PNETs for the mutation and/or expression of SMOH, PTCH, SHH, 
      and GL11. In addition, we fine-mapped the SMOH gene locus by fluorescence in situ 
      hybridization to chromosomal band 7q32. Mutational analysis identified four BCCs 
      with somatic missense mutations in SMOH affecting codon 535 (TGG==>TTG: 
      Trp==>Leu) in three tumors and codon 199 (CGG==>TGG: Arg==>Trp) in one tumor. A 
      missense mutation at codon 533 (AGC==>AAC: Ser==>Asn) was found in one PNET. PTCH 
      mutations were detected in eight BCCs and one PNET. Two BCCs demonstrated 
      mutations in both SMOH and PTCH. The majority of tumors showed an increased 
      expression of SMOH, PTCH, and GL11 transcripts as compared with that of normal 
      skin and nonneoplastic brain tissue, respectively. In contrast, only one BCC and 
      one PNET expressed SHH mRNA at levels detectable by reverse transcription-PCR, 
      and no SHH gene mutations were found. In summary, our results indicate that both 
      PTCH and SMOH represent important targets for genetic alterations in sporadic 
      BCCs and PNETs.
FAU - Reifenberger, J
AU  - Reifenberger J
AD  - Hautklinik, Heinrich-Heine-Universitat, Dusseldorf, Germany.
FAU - Wolter, M
AU  - Wolter M
FAU - Weber, R G
AU  - Weber RG
FAU - Megahed, M
AU  - Megahed M
FAU - Ruzicka, T
AU  - Ruzicka T
FAU - Lichter, P
AU  - Lichter P
FAU - Reifenberger, G
AU  - Reifenberger G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SHH protein, human)
RN  - 0 (SMO protein, human)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Brain Neoplasms/*genetics/metabolism
MH  - Carcinoma, Basal Cell/*genetics/metabolism
MH  - Child
MH  - Child, Preschool
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 7/genetics
MH  - DNA Mutational Analysis
MH  - DNA Primers/chemistry
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Hedgehog Proteins
MH  - Humans
MH  - Infant
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Middle Aged
MH  - Neuroectodermal Tumors, Primitive/*genetics/metabolism
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - *Point Mutation
MH  - Proteins/*genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Cell Surface/*genetics/metabolism
MH  - *Receptors, G-Protein-Coupled
MH  - Skin Neoplasms/*genetics/metabolism
MH  - Smoothened Receptor
MH  - *Trans-Activators
EDAT- 1998/05/15 00:00
MHDA- 1998/05/15 00:01
CRDT- 1998/05/15 00:00
PHST- 1998/05/15 00:00 [pubmed]
PHST- 1998/05/15 00:01 [medline]
PHST- 1998/05/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1998 May 1;58(9):1798-803.